Deletion of the vaccinia virus B1 kinase reveals essential functions of this enzyme complemented partly by the homologous cellular kinase VRK2

Annabel T. Olson, Amber B. Rico, Zhigang Wang, Gustavo Delhon, Matthew S. Wiebe

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The vaccinia virus B1 kinase is highly conserved among poxviruses and is essential for the viral life cycle. B1 exhibits a remarkable degree of similarity to vaccinia virus-related kinases (VRKs), a family of cellular kinases, suggesting that the viral enzyme has evolved to mimic VRK activity. Indeed, B1 and VRKs have been demonstrated to target a shared substrate, the DNA binding protein BAF, elucidating a signaling pathway important for both mitosis and the antiviral response. In this study, we further characterize the role of B1 during vaccinia infection to gain novel insights into its regulation and integration with cellular signaling pathways. We begin by describing the construction and characterization of the first B1 deletion virus (vvΔB1) produced using a complementing cell line expressing the viral kinase. Examination of vvΔB1 revealed that B1 is critical for the production of infectious virions in various cell types and is sufficient for BAF phosphorylation. Interestingly, the severity of the defect in DNA replication following the loss of B1 varied between cell types, leading us to posit that cellular VRKs partly complement for the absence of B1 in some cell lines. Using cell lines devoid of either VRK1 or VRK2, we tested this hypothesis and discovered that VRK2 expression facilitates DNA replication and allows later stages of the viral life cycle to proceed in the absence of B1. Finally, we present evidence that the impact of VRK2 on vaccinia virus is largely independent of BAF phosphorylation. These data support a model in which B1 and VRK2 share additional substrates important for the replication of cytoplasmic poxviruses.

Original languageEnglish (US)
Article numbere00635-17
JournalJournal of virology
Volume91
Issue number15
DOIs
StatePublished - Aug 1 2017

Keywords

  • B1R
  • BAF
  • BANF1
  • Poxviruses
  • Protein kinases
  • VRK2
  • Vaccinia

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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